This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. HIV and SIV have evolved alternative countermeasures to overcome restriction by tetherin, an interferon-inducible cellular factor that inhibits the release of virus particles from infected cells. We identified compensatory genetic changes in a pathogenic derivative of a nef-deleted vaccine strain of simian immunodeficiency virus that restore resistance to tetherin. These observations suggest that the ability to overcome restriction by tetherin is important for AIDS-virus pathogenesis.